Genetic Variant GNAQ:c.735+34T>C (chr9-77794429-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002072.5(GNAQ):c.735+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,438,706 control chromosomes in the GnomAD database, including 207,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 16258 hom., cov: 31)

Exomes 𝑓: 0.53 ( 190778 hom. )

Consequence

GNAQ
NM_002072.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.605

Variant links:

Genes affected

GNAQ (HGNC:4390): (G protein subunit alpha q) This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]

GNAQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-77794429-A-G is Benign according to our data. Variant chr9-77794429-A-G is described in ClinVar as [Benign]. Clinvar id is 1234387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GNAQ	NM_002072.5 link	c.735+34T>C	intron_variant	Intron 5 of 6	ENST00000286548.9	NP_002063.2	P50148A0A024R240
GNAQ	XM_047423239.1 link	c.561+34T>C	intron_variant	Intron 5 of 6		XP_047279195.1
GNAQ	XM_047423240.1 link	c.561+34T>C	intron_variant	Intron 5 of 6		XP_047279196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAQ	ENST00000286548.9 link	c.735+34T>C		intron_variant	Intron 5 of 6	1	NM_002072.5	ENSP00000286548.4		P50148

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64389

AN:

151826

Hom.:

16260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.451

GnomAD2 exomes

AF:

0.481

AC:

105929

AN:

220078

AF XY:

0.492

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.535

Gnomad EAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.534

AC:

686926

AN:

1286762

Hom.:

190778

Cov.:

AF XY:

0.533

AC XY:

343038

AN XY:

643084

show subpopulations

African (AFR)

AF:

0.131

AC:

3893

AN:

29628

American (AMR)

AF:

0.456

AC:

17369

AN:

38102

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

12336

AN:

23448

East Asian (EAS)

AF:

0.221

AC:

8207

AN:

37096

South Asian (SAS)

AF:

0.438

AC:

31794

AN:

72648

European-Finnish (FIN)

AF:

0.503

AC:

25229

AN:

50108

Middle Eastern (MID)

AF:

0.478

AC:

1787

AN:

3742

European-Non Finnish (NFE)

AF:

0.572

AC:

559095

AN:

977958

Other (OTH)

AF:

0.504

AC:

27216

AN:

54032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

13126

26253

39379

52506

65632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.424

AC:

64381

AN:

151944

Hom.:

16258

Cov.:

AF XY:

0.419

AC XY:

31122

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.152

AC:

6316

AN:

41486

American (AMR)

AF:

0.474

AC:

7239

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1863

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1143

AN:

5158

South Asian (SAS)

AF:

0.420

AC:

2021

AN:

4812

European-Finnish (FIN)

AF:

0.490

AC:

5171

AN:

10554

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38925

AN:

67892

Other (OTH)

AF:

0.448

AC:

946

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1624

3248

4871

6495

8119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.524

Hom.:

20319

Bravo

AF:

0.409

Asia WGS

AF:

0.307

AC:

1072

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr9-77794429-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over